Dramatic Response to Pramipexole in Delayed-Onset Parkinsonism from Osmotic Demyelinating Syndrome.

Background: Delayed parkinsonism and dystonia are recognized phenomena in osmotic demyelinating syndrome (ODS). Dopamine receptor agonists and levodopa have been reported to benefit select patients. Case report: We report a patient with ODS with severe pseudobulbar deficits, parkinsonism and dystonia, poorly responsive to levodopa, who experienced a remarkable improvement with pramipexole. Discussion: A marked response to pramipexole with lack of response to levodopa suggests a pre-synaptic source for his deficits coupled with injuries to non-nigral compensatory structures. Highlights: This case highlights a dramatic response of osmotic demyelination-induced parkinsonism/dystonia to pramipexole. A lack of response to levodopa suggests deficits in the pre-synaptic nigral as well as non-nigral compensatory structures.

Central Pontine Myelinosis and Osmotic Demyelination Syndrome.

BACKGROUND: Osmotic demyelination syndrome (ODS), which embraces central pontine myelinolysis (CPM) and extrapontine myelinosis (EPM), is often underdiagnosed in clinical practice, but can be fatal. In this article, we review the etiology, patho- physiology, clinical features, diagnosis, treatment, and prognosis of ODS. METHODS: Pertinent publications from the years 1959 to 2018 were retrieved by a selective search in PubMed. RESULTS: The most common cause of ODS is hyponatremia; particular groups of patients, e.g., liver transplant recipients, are also at risk of developing ODS. The pathophysiology of ODS consists of cerebral apoptosis and loss of myelin due to osmotic stress. Accordingly, brain areas that are rich in oligodendrocytes and myelin tend to be the most frequently affected. Patients with ODS often have a biphasic course, the first phase reflecting the underlying predisposing illness and the second phase reflecting ODS itself, with pontine dysfunction, impaired vigilance, and movement disorders, among other neurological abnormalities. The diagnostic modality of choice is magnetic resonance imaging (MRI) of the brain, which can also be used to detect oligosymptomatic ODS. The current mainstay of management is prevention; treatment strategies for manifest ODS are still experimental. The prognosis has improved as a result of MRI-based diagnosis, but ODS can still be fatal (33% to 55% of patients either die or remain permanently dependent on nursing care). CONCLUSION: ODS is a secondary neurological illness resulting from a foregoing primary disease. Though rare overall, it occurs with greater frequency in certain groups of patients. Clinicians of all specialties should therefore be familiar with the risk constellations, clinical presentation, and prevention of ODS. The treatment of ODS is still experimental at present, as no evidence-based treatment is yet available.

Osmotic Demyelination Syndrome in Children.

Osmotic demyelination syndrome is an acute demyelination process that usually occurs several days following an osmotic stress. This syndrome is rare in adults (0.4% to 0.56%) and even more uncommon in children. We performed a review of all reported pediatric osmotic demyelination syndrome patients from 1960 to 2018. Among all 106 cases, 49 presented with isolated central pontine myelinolysis, 30 with isolated extrapontine myelinolysis, and 27 with combined central pontine myelinolysis and extrapontine myelinolysis. There was no gender preponderance, and the highest prevalence was noted between the ages one and five years. Magnetic resonance imaging remains the diagnostic modality of choice, and diffusion tensor imaging is now increasingly used for prognostication in osmotic demyelination syndrome. Sixty percent of the children had a complete neurological recovery. Current management of osmotic demyelination syndrome in children consists of supportive medical care, steroids, and intravenous immunoglobulin. Our review of the literature supports the hypothesis that steroids and immunoglobulins are potentially helpful, although additional controlled studies are needed.

Short-course metronidazole-induced reversible acute neurotoxicity in a renal transplant recipient.

Neurotoxic manifestations due to chronic metronidazole intake are well known, but neurotoxicity due to short-term use of metronidazole is very rare. We present a case of acute neurotoxicity due to short course of injectable metronidazole given in usual doses to a renal allograft recipient for persistent diarrhea. It responded to withdrawal of the offending drug. Tacrolimus trough concentration did not increase during neurotoxicity, thereby ruling out any metronidazole-tacrolimus interaction. Magnetic resonance imaging of the brain showed widespread osmotic demyelination and its recovery after drug withdrawal. This is the first reported case of a renal transplant recipient developing acute neurotoxicity due to short-term use of metronidazole, without any increase in tacrolimus trough concentrations.

Osmotic Demyelination Syndrome Revisited: Review With Neuroimaging.

Osmotic demyelination syndrome (ODS) is a general term that has become commonplace in the practice of medicine, encompassing both central pontine myelinolysis and extrapontine myelinolysis. Historically ODS arises as a serious complication of rapid correction of hyponatremia, yet its manifestations seem to be influenced by a multifactorial process. Further understanding of this rare demyelinating disease has elucidated the significant role of other electrolyte disturbances and the presence of chronic comorbidities as disease risk factors. This review discusses the current research regarding the pathophysiology, clinical manifestations, neuroimaging features, patient management, and prognosis of osmotic demyelination syndrome. We hope that this review will further endorse and aid in the proper diagnosis of ODS and its suitable management through the understanding of clinical and imaging correlations and outcomes, and the comorbid factors that may predispose the development of ODS in certain patient populations.

Mielinólisis pontina y extrapontina secundaria a fluctuaciones en la glucemia / Pontine and extrapontine myelinolysis secondary to glycemic fluctuati

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Evidence of aquaporin involvement in human central pontine myelinolysis.

BACKGROUND: Central pontine myelinolysis (CPM) is a demyelinating disorder of the central basis pontis that is often associated with osmotic stress. The aquaporin water channels (AQPs) have been pathogenically implicated because serum osmolarity changes redistribute water and osmolytes among various central nervous system compartments. RESULTS: We characterized the immunoreactivity of aquaporin-1 and aquaporin-4 (AQP1 and AQP4) and associated neuropathology in microscopic transverse sections from archival autopsied pontine tissue from 6 patients with pathologically confirmed CPM. Loss of both AQP1 and AQP4 was evident within demyelinating lesions in four of the six cases, despite the presence of glial fibrillary acidic protein (GFAP)-positive astrocytes. Lesional astrocytes were small, and exhibited fewer and shorter processes than perilesional astrocytes. In two of the six cases, astrocytes within demyelinating lesions exhibited increased AQP1 and AQP4 immunoreactivities, and gemistocytes and mitotic astrocytes were numerous. Blinded review of medical records revealed that all four cases lacking lesional AQP1 and AQP4 immunoreactivities were male, whereas the two cases with enhanced lesional AQP1 and AQP4 immunoreactivities were female. CONCLUSIONS: This report is the first to establish astrocytic AQP loss in a subset of human CPM cases and suggests AQP1 and AQP4 may be involved in the pathogenesis of CPM. Further studies are required to determine whether the loss of AQP1 and AQP4 is restricted to male CPM patients, or rather may be a feature associated with specific underlying precipitants of CPM that may be more common among men. Non-rodent experimental models are needed to better clarify the complex and dynamic mechanisms involved in the regulation of AQPs in CPM, in order to determine whether it occurs secondary to the destructive disease process, or represents a compensatory mechanism protecting the astrocyte against apoptosis.

Central pontine myelinolysis in a chronic alcoholic: a clinical and brain magnetic resonance imaging follow-up.

INTRODUCTION: Central pontine myelinolysis (CPM) is a noninflammatory, demyelinating lesion usually localised in the basis pontis. Chronic alcoholism is frequently associated with this condition which may have a variable clinical outcome. Until now, brain magnetic resonance imaging (MRI) follow-up in alcoholic CPM cases after alcohol withdrawal has been rarely described. CASE REPORT: We reported a 30-year-old male with a 12-year history of alcohol abuse, who presented with inability to stand and walk, nausea, vomiting and somnolence. Neurological examination revealed: impared fixation on lateral gaze, dysarthria, mild spastic quadriparesis, truncal and extremity ataxia, sock-like hypesthesia and moderate decrease in vibration sense in legs. Brain MRI showed a trident-shaped non-enhancing pontine lesion highly suggestive of CPM. After an eight-month alcohol-free follow-up period, the patient's clinical status significantly improved, while the extent of MRI pontine lesion was merely slightly reduced. CONCLUSION: The presented case demonstrates that CPM in chronic alcoholics may have a benign clinical course after alcohol withdrawal, which is not necessarily associated with the reduction of lesions on brain MRI.

[Central pontin myelinolysis]. / Central pontinmyelinolyse og hyponatriæmi.

Initially central pontin myelinolysis was associated with alcoholism and later with hyponatraemia and particularly the correction rate. The diagnosis is made by characteristic symptoms and cerebral MRI with areas of hyperintensity on T2-weighted images. Outcome varies, mortality is high and most survivors have some degree of neurological deficit. There is no treatment and supportive therapy remains the only option with possible recovery within 6-8 weeks. Hyponatraemia can safely be corrected at a rate of no more than 10 mmol/l within the first 24 hours and 18 mmol/l within 48 hours.

Movement disorders and the osmotic demyelination syndrome.

With the advent of MRI, osmotic demyelination syndromes (ODS) are increasingly recognised to affect varied sites in the brain in addition to the classical central pontine lesion. Striatal involvement is seen in a large proportion of cases and results in a wide variety of movement disorders. Movement disorders and cognitive problems resulting from ODS affecting the basal ganglia may occur early in the course of the illness, or may present as delayed manifestations after the patient survives the acute phase. Such delayed symptoms may evolve over time, and may even progress despite treatment. Improved survival of patients in the last few decades due to better intensive care has led to an increase in the incidence of such delayed manifestations of ODS. While the outcome of ODS is not as dismal as hitherto believed - with the acute akinetic-rigid syndrome associated with striatal myelinolysis often responding to dopaminergic therapy - the delayed symptoms often prove refractory to medical therapy. This article presents a review of the epidemiology, pathophysiology, clinical features, imaging, and therapy of movement disorders associated with involvement of the basal ganglia in ODS. A comprehensive review of 54 previously published cases of movement disorders due to ODS, and a video recording depicting the spectrum of delayed movement disorders seen after recovery from ODS are also presented.

Clinical and functional outcome and factors predicting prognosis in osmotic demyelination syndrome (central pontine and/or extrapontine myelinolysis) in 25 patients.

AIMS: To assess the functional and clinical outcome in a sizeable cohort of patients with osmotic demyelination syndrome (ODS) and to characterise the factors which could predict the final outcome. METHODS: Twenty five consecutive patients with ODS formed the study cohort. The diagnosis of ODS was based on clinical features with corroborating imaging findings. Two functional scales--Functional Independent Measure (FIM) and Disability Rating Scale (DRS)--were applied to assess the functional status at the time of admission, discharge and last follow-up. Patients who became independent for activities of daily living (ADL) at last follow-up were classified as favourable outcome, and those who died or became dependent for ADL were classified as a poor outcome group respectively. The Fisher exact test and Mann-Whitney U test were used to assess categorical and continuous variables respectively. RESULTS: The mean age at diagnosis was 53 ± 14 years. Five (20%) had central pontine myelinolysis, seven (28%) had extrapontine myelinolysis, and 13 (52%) had both. Hyponatraemia and hypokalaemia were noted in 20 (80%) and 10 (40%) patients respectively. Six (24%) received intravenous methylprednisolone. Eleven (46%) had a favourable outcome at a mean follow-up of 2.2 ± 2.5 years. Hyponatraemia ≤ 115 mEq (p=0.04), associated hypokalaemia (p=0.04) and low Glasgow Coma Scale (GCS) (p=0.008) at presentation were predictive of poor outcome. The mean FIM score at admission (p=0.05) and at discharge (p=0.01), and mean DRS at admission (p=0.05) were predictive of poor outcome. CONCLUSIONS: Higher GCS scores, better scores in functional scales in hospital, less severe hyponatraemia and absence of superadded hypokalaemia predicted favourable outcome.

A case of asymptomatic pontine myelinolysis.

Central pontine myelinolysis is an acquired, non-inflammatory demyelinating lesion usually localized in the brainstem pons basis; it usually affects patients with a history of chronic alcoholism, malnutrition or dysionemia. The exact pathogenesis of myelinolysis is still unclear. A 69-year-old Caucasian male presented intensive headache and underwent cranial MRI that showed the typical feature of central pontine myelinolysis. Neurological valuation was negative. Other examinations included extensive blood tests, electroencephalogram and multimodal evoked potentials which all gave normal results. Alcohol abuse and malabsorption syndrome were excluded. The medical history revealed a continuative use of anti-depressive drugs and exposure to glue for years. Our patient may represent one of the rare cases of asymptomatic CPM. The actual reason why he presented this lesion is not clear, but we discuss the possible role in the etiopathogenesis of his chronic use of anti-depressive drugs and the exposure to glue and chemical agents.